In Situ Precipitation of Amorphous Calcium Phosphate and Ciprofloxacin Crystals during the Formation of Chitosan Hydrogels and Its Application for Drug Delivery Purposes

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• 作者：Stefania Nardecchia ; Mar铆a C. Guti茅rrez ; M. Concepci贸n Serrano ; Mariella Dentini ; Andrea Barbetta ; M. Luisa Ferrer ; Francisco del Monte
• 刊名：Langmuir
• 出版年：2012
• 出版时间：November 13, 2012
• 年：2012
• 卷：28
• 期：45
• 页码：15937-15946
• 全文大小：633K
• 年卷期：v.28,no.45(November 13, 2012)
• ISSN：1520-5827

文摘

The immobilization of more than one single substance within the structure of a biocompatible polymer provides multifunctional biomaterials with attractive and enhanced properties. In the context of bone tissue engineering, it could be of great interest to synthesize a biomaterial that simultaneously contains amorphous calcium phosphate (ACP), to favor calcium and phosphate precipitation and promote osteogenesis, and an antibiotic such as ciprofloxacin (CFX) that can, eventually, avoid infections resulting after surgical scaffold implantation. However, the co-immobilization of multiple substances is by no means a trivial issue because of the enhanced number of interactions that can take place. One of the main issues is controlling not only the diverse solid forms that individual substances can eventually adopt, but also the forces responsible for the self-organization of the individual components. The latter determines whether phase-separated structures or conjugated architectures are obtained and, consequently, may dramatically affect their functionality. Herein, we have observed鈥攂y SEM, TEM, and solid-state NMR鈥攖hat enzymatically-assisted coprecipitation of ACP and CFX resulted in phase-separated structures. Thus, CFX crystals showed identical morphology to that obtained in the absence of ACP, but the size was smaller. Neither the size nor the morphology of ACP exhibited significant differences whether precipitated with or without CFX, but, in the former case, ACP was stabilized over a wider range of pH and temperature. Finally, by using this methodology and the ice segregation induced self-assembly process (ISISA), we have successfully co-immobilized ACP and CFX in chitosan-based scaffolds. Interestingly, the presence of ACP exerted significant control on the CFX release from these materials.